The goal of this research is to identify valid, reproducible and noninvasive methods for biologically monitoring occupational methanol exposure, and to assess quantitively the impact of exercise and cutaneous methanol exposure on such indices. The underlying approach will be to perform a series of controlled experiments with volunteer subjects. Specific aims are to investigate the: 1. Use of formic acid (formate) in urine as a quantitative biological exposure indicator for exposure of humans to methanol via the inhalation route and via the cutaneous route; 2. Use of methanol in urine as a quantitative biological exposure indicator for exposure of humans to methanol via the inhalation route and via the cutaneous route; 3. Use of methanol in end-expired (alveolar) air as a quantitative biological exposure indicator for exposure of humans to methanol via the inhalation route and via the cutaneous route; 4. Effect of exercise, as measured by the ventilation rate, on formic acid in urine, methanol in urine and methanol in end-expired air when humans are exposed to methanol via the inhalation route. Methanol has been selected by the U.S. government as a primary candidate for promotion as an alternative automotive fuel. Usage as an automotive fuel would involve vastly greater opportunities for chronic low-level exposure of workers and consumers to methanol than have existed in the past. Human health effects related to chronic, low-level methanol exposure are largely unknown. There have been no human epidemiologic studies focused on the effects of chronic low-level methanol exposure, and results of animal studies are difficult to extrapolate to humans because of significant differences in the metabolism and toxicity of methanol in most animal models. An essential component of any human epidemiologic investigation of the effects of chronic low-level methanol exposure will be exposure assessment of subjects. Methanol is quite well absorbed via all major routes of exposure (gastrointestinal, inhalational, and dermal), so biological indicators of methanol exposure would provide more accurate assessment of the total absorbed dose, in comparison to routine measurements of the airborne concentration of methanol that are usually applied in the industrial setting. Although two approaches to biological monitoring of occupational methanol exposure have been endorsed by the ACGIH, the published data supporting these methods are limited, and in some areas, are contradicted by more recent reports. The data and analyses from this study will permit separate, quantitative examination of the major factors which are believed to influence biological indicators of methanol exposure in the occupational setting: airborne concentration of exposure; duration of exposure; level of pulmonary ventilation; and cutaneous exposure.